Editors' ChoiceMyocardial Infarction

How Does the Heart Heal?

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Science Translational Medicine  21 May 2014:
Vol. 6, Issue 237, pp. 237ec91
DOI: 10.1126/scitranslmed.3009314

Suffering a heart attack is a life-changing event. Adding to patients’ unease is the inability of their doctors to predict whether their heart will heal or progressively deteriorate. Although cardiologists can often make rough predictions, little definitive guidance is possible until several months have elapsed. This uncertainty is only partially driven by clinical circumstances; there are many uncharacterized pathophysiological factors at play in the days, weeks, and months after a heart attack. Heart remodeling is known to be influenced by reprogramming of the cardiac gene regulatory network in response to physiological stress, but the factors that drive reprogramming are unknown. Now, Ounzain et al. investigate factors that modulate cardiac gene regulation in a mouse model of myocardial infarction.

Regulation of gene expression was once considered to be a fairly simple process, with RNA involved primarily as a passive intermediary for the translation of DNA into proteins. Over time, scientists have learned that RNA that is not translated into protein—so-called noncoding RNA—can dynamically regulate gene transcription and posttranscriptional processing. Of the many forms of noncoding RNA, long noncoding RNAs (lncRNAs) are one of the most common and least understood.

Ounzain et al. undertook an extensive evaluation of factors that affect cardiac gene regulation in mice after an experimentally induced myocardial infarction. They found lncRNA transcription patterns that were well correlated with specific adverse cardiac changes and identified related DNA segments in the human genome that could encode similar lncRNAs. Their work established that there are distinct patterns of lncRNA transcription in areas of the heart that are adjacent to versus distant from the infarction, as well as different temporal patterns of lncRNA transcription after a heart attack. Subsequent research may identify lncRNAs that serve as markers of adverse outcomes or targets for new myocardial infarction treatments that regulated cardiac remodeling.

S. Ounzain et al., Genome-wide profiling of the cardiac transcriptome after myocardial infarction identifies novel heart-specific non-coding RNAs. Eur. Heart J. 10.1093/eurheartj/ehu180 (2014). [Abstract]

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